Impact of the COVID-19 pandemic on community-dwelling older adults: A longitudinal qualitative study of participants from the Hertfordshire Cohort Study.

BACKGROUND: Older adults have been especially vulnerable to adverse effects from the COVID-19 pandemic including higher mortality and more severe disease complications. At the same time, social isolation, malnutrition and physical inactivity are serious concerns among older adults. The pandemic and associated restrictions may serve to exacerbate these issues, presenting increased risks to physical and mental health. The aims of this qualitative study were: i) to explore how community-living older people in the UK experienced the first wave of the COVID-19 pandemic, specifically how it impacted their well-being and associated health behaviours; ii) to explore how older people's experiences and behaviours changed over time throughout the first wave. METHODS: Qualitative data were collected by conducting serial telephone interviews, with an interval of approximately three months. Participants were from the Hertfordshire Cohort Study, all aged over 80 years. Discussions were audio-recorded, information related to the COVID-19 pandemic was transcribed verbatim and transcripts analysed thematically. Interviews were conducted from March to October 2020. RESULTS: Data for twelve participants (7 men and 5 women) from a total of 35 interviews were used, comprising two or three timepoints per participant. Analysis identified five overarching themes: 1) shopping strategies and food accessibility, 2) limitations on activities and going out, 3) disruption to healthcare, 4) social and psychological repercussions, and 5) coping strategies. Findings highlight challenges associated with accessing shops, healthcare, and usual activities due to pandemic-related restrictions. Longitudinal findings showed that for some, the ongoing pandemic and related restrictions appeared to aggravate mental health issues (low mood, anxiety) over time, as well as greater feelings of isolation or loneliness, reduced activity and functional limitations; this was despite some relaxation of restrictions later on. Coping strategies used by participants included finding ways to keep busy and to do physical activity safely, maintaining social contact remotely, and having an optimistic or positive outlook, a 'do what you can' attitude. CONCLUSIONS: Interventions are likely to be needed in the wake of the COVID-19 pandemic to support health behaviours, such as increasing physical activity, social engagement and improving mental health among community-living older adults.

Controlled and Selective Photo-oxidation of Amyloid-ß Fibrils by Oligomeric p-Phenylene Ethynylenes.

Photodynamic therapy (PDT) has been explored as a therapeutic strategy to clear toxic amyloid aggregates involved in neurodegenerative disorders such as Alzheimer's disease. A major limitation of PDT is off-target oxidation, which can be lethal for the surrounding cells. We have shown that a novel class of oligo-p-phenylene ethynylenes (OPEs) exhibit selective binding and fluorescence turn-on in the presence of prefibrillar and fibrillar aggregates of disease-relevant proteins such as amyloid-ß (Aß) and α-synuclein. Concomitant with fluorescence turn-on, OPE also photosensitizes singlet oxygen under illumination through the generation of a triplet state, pointing to the potential application of OPEs as photosensitizers in PDT. Herein, we investigated the photosensitizing activity of an anionic OPE for the photo-oxidation of Aß fibrils and compared its efficacy to the well-known but nonselective photosensitizer methylene blue (MB). Our results show that, while MB photo-oxidized both monomeric and fibrillar conformers of Aß40, OPE oxidized only Aß40 fibrils, targeting two histidine residues on the fibril surface and a methionine residue located in the fibril core. Oxidized fibrils were shorter and more dispersed but retained the characteristic ß-sheet rich fibrillar structure and the ability to seed further fibril growth. Importantly, the oxidized fibrils displayed low toxicity. We have thus discovered a class of novel theranostics for the simultaneous detection and oxidization of amyloid aggregates. Importantly, the selectivity of OPE's photosensitizing activity overcomes the limitation of off-target oxidation of traditional photosensitizers and represents an advancement of PDT as a viable strategy to treat neurodegenerative disorders.

Impact of Menopausal Symptoms on Work: Findings from Women in the Health and Employment after Fifty (HEAF) Study.

Women make up a growing proportion of the workforce and therefore many women experience menopause while in paid employment. We explored the prevalence of menopausal symptoms, the relationship between symptoms and coping with work and the risk factors associated with struggling at work during the menopause. The Health and Employment After Fifty (HEAF) community-based cohort of people aged 50-64 years was incepted 2013-2014 to study health and work. In 2019, female participants were asked to complete a questionnaire about their menopausal symptoms, and effect of those symptoms on their ability to cope at work. 409 women were eligible for inclusion. The commonest symptoms were vasomotor (91.7%); trouble sleeping (68.2%); psychological (63.6%) and urinary (49.1%). The prevalence of reporting symptoms was similar no matter which type of occupation women were performing at the time. Around one-third of women reported moderate/severe difficulties coping at work because of menopausal symptoms. Risk factors for difficulties coping at work included: financial deprivation, poorer self-rated health, depression, and adverse psychosocial occupational factors but not physical demands. More awareness is needed amongst employers in all sectors but women with financial difficulties and those with jobs in which they feel insecure, unappreciated, or dissatisfied are at greatest risk.

Use and Toxicity of Checkpoint Inhibitors for Solid Tumor Treatment in a Veteran Population.

BACKGROUND: New immunotherapy agents have provided additional options for the treatment of a variety of malignancies, including the programmed death 1 (PD-1) protein inhibitors nivolumab and pembrolizumab. Initial dosing was based on patient weight, but subsequent studies supported fixed dosing, thereby prompting a change in US Food and Drug Administration-approved dosing. Depending on patient weight, one dosing strategy may be more cost-effective than another; thereby, a combination of dosing strategies may be beneficial for institutions. While these agents have been shown to be efficacious, they have been associated with immune-related adverse events (IrAEs). The purpose of this study was to determine the dosing strategy used and identify actual and potential cost savings, as well as to determine the incidence of hypothyroidism with PD-1 inhibitors in patients of the US Department of Veterans Affairs (VA). METHODS: This was a retrospective chart review of VA patients who received a PD-1 inhibitor for the treatment of a solid tumor between January 2015 and July 2017. Data were collected from the VA Corporate Data Warehouse through the VA Informatics and Computing Infrastructure. The dosing strategy for a PD-1 inhibitor was categorized into weight-based vs fixed-dosing where possible and used to identify actual and potential cost-savings opportunities. Thyroid laboratory values and levothyroxine prescriptions were evaluated to determine the overall incidence of the prespecified IrAEs. Descriptive statistics were used for primary and secondary outcomes. RESULTS: Nivolumab was the primary PD-1 inhibitor used for solid tumor treatment. Both nivolumab and pembrolizumab were primarily dosed based on patient weight. Nivolumab orders resulted in $8,514,300 estimated actual cost savings with $5,591,250 estimated missed cost savings identified. Of the patients who received nivolumab, 3249 patients were evaluated for thyroid dysfunction; 514 (15.8%) developed primary hypothyroidism based on laboratory values and levothyroxine prescription data. CONCLUSIONS: Utilization of a combination of both weight-based and fixed-dosing strategies for nivolumab has the potential for cost savings, thereby benefiting the health care institution. The incidence of IrAEs identified among patients who received PD-1 inhibitor within the VA health care system was similar to the incidences reported in published literature. This further supports recommendations for close IrAE monitoring and treatment.

Cryotherapy for the prevention of chemotherapy-induced peripheral neuropathy: A systematic review.

OBJECTIVE: Chemotherapy induced peripheral neuropathy (CIPN) is an adverse effect of certain chemotherapy agents that can result in dose reductions, permanent nerve damage, and chronic pain. Although pharmacological agents have been studied in this setting, there is no standard of care for the prevention of CIPN. Thus, the objective of this systematic review is to assess the efficacy and safety of cryotherapy for the prevention of CIPN. DATA SOURCES: PubMed (1946 to February 2020) and Embase (1947 to February 2020) were utilized to conduct a literature search using the following search terms: antineoplastic agent(s), taxoid(s), or chemotherapy and neuralgia, peripheral nervous system diseases, peripheral neuropathy, or paclitaxel-induced peripheral neuropathy and cryotherapy, cryotherapy device, hypothermia, low temperature procedures, or ice. DATA SUMMARY: A total of 11 studies were included in the final assessment. Results of this systematic review indicate that the efficacy of cryotherapy in preventing CIPN is conflicting. This may be due to studies utilizing differing cryotherapy administration methods, study design, and including only a small number of patients. All included studies utilized cryotherapy with taxane-based chemotherapy treatments and cooling gloves and socks was the most common method of administration. Overall, cryotherapy was well-tolerated and no serious adverse effects were noted. CONCLUSIONS: Due to the absence of serious adverse effects, cryotherapy is a reasonable option to consider to prevent CIPN in patients receiving taxane-based chemotherapy. However, additional research is needed, including larger, better designed studies, to fully delineate the role of cryotherapy for CIPN.

Measured weight in early pregnancy is a valid method for estimating pre-pregnancy weight.

Estimation of pre-pregnancy weight is difficult because measurements taken before pregnancy are rarely available. No studies have compared various 'proxy' measures using recalled weight or based on early pregnancy weight with actual measurements of pre-pregnancy weight. The Southampton Women's Survey recruited women during 1998-2002 who were not pregnant. Data on 198 women with an estimated date of conception within 3 months of recruitment were analysed. Three proxy measures were considered: (1) recalled pre-pregnancy weight obtained during early pregnancy, (2) measured weight in early pregnancy and (3) estimated pre-pregnancy weight using a published model. Mean (standard deviation) recalled weight was 1.65 (3.03) kg lighter than measured pre-pregnancy weight, while early pregnancy weight and weights from the published model were 0.88 (2.34) and 0.88 (2.33) kg heavier, respectively. The Bland-Altman limits of agreement for recalled weight were -7.59 to 4.29 kg, wider than those for the early pregnancy weight: -3.71 to 5.47 kg and the published model: -3.68 to 5.45 kg. For estimating pre-pregnancy weight, we recommend subtraction of 0.88 kg from early pregnancy weight or the published model, or addition of 1.65 kg to recalled weight. Estimates of pre-pregnancy body mass index and gestational weight gain categories were very similar when using early pregnancy and published model weights, but they differed from those using recalled weight. Our findings indicate that calculations of first trimester weight gain using recalled weight must be treated cautiously, and a measured weight in early pregnancy provides a more precise assessment of pre-pregnancy weight than recalled weight.

How can we best use opportunities provided by routine maternity care to engage women in improving their diets and health?

Pregnancy provides motivation for women to improve their diets and increase their physical activity. Opportunistic brief interventions delivered as part of routine primary care have produced improvements in patients' health behaviour. Consequently, there have been calls for midwives to use contacts during pregnancy in this way. This study explored the experiences of pregnant women and research midwives/nurses of a brief intervention called Healthy Conversation Skills (HCS) being delivered as part of a randomised control trial, assessing the acceptability and feasibility of including this intervention in routine maternity care. Three research questions were addressed using mixed methods to produce four datasets: face-to-face interviews with participants, a focus group with the HCS-trained midwives/nurses, case reports of participants receiving HCS and audio-recordings of mid-pregnancy telephone calls to the women which produced midwife/nurse HCS competency scores. Midwives/nurses used their HCS to support women to make plans for change and set goals. Women welcomed the opportunity to address their own health and well-being as distinct from that of their baby. Midwives/nurses were competent in using the skills and saw healthy conversations as an effective means of raising issues of diet and physical activity. Recent extension of maternity appointment times provides ideal opportunities to incorporate a brief intervention to support behaviour change. Incorporating HCS training into midwifery education and continuing professional development would facilitate this. HCS is a scalable, brief intervention with the potential to improve the diets and physical activity levels of women during pregnancy, and hence the health of themselves and their babies.

The Role of Pazopanib in Non-Clear Cell Renal Cell Carcinoma: A Systematic Review.

Pazopanib is a protein tyrosine kinase inhibitor that limits tumor growth through angiogenesis inhibition. The use of other protein tyrosine kinase inhibitors, specifically sunitinib, within non-clear cell renal cell carcinoma (nccRCC) has led to increased survival with a decreased adverse event profile. The data for the treatment of nccRCC is limited, with most studies evaluating the use of sunitinib. Therefore, the evaluation of pazopanib is of particular clinical interest in the treatment of nccRCC. The objective of this systematic review was to assess the efficacy and safety of pazopanib for nccRCC. PubMed (1946 to April 2019) and Embase (1947 to April 2019) were queried using the search term combination: protein tyrosine kinase inhibitor or pazopanib and non clear cell renal cell carcinoma or non-clear cell renal cell carcinoma. Studies evaluating clinical outcomes of pazopanib for nccRCC were included, represented by 3 retrospective cohort studies and 1 single-arm, open-label prospective study. In patients with advanced or metastatic nccRCC, treatment with pazopanib resulted in positive effects for multiple markers of efficacy, including progression-free survival, overall survival, and objective response rates. The median duration of follow-up ranged from 11.8 months to 24.4 months. Pazopanib was well-tolerated in most studies. The most commonly reported adverse events were fatigue, diarrhea, and hypertension. Pazopanib appears to be an effective and safe option for the treatment of advanced or metastatic nccRCC. Future investigation with larger randomized controlled trials is warranted to further define the role of pazopanib in patients with nccRCC.

Preventing Hepatitis B Reactivation During Anti-CD20 Antibody Treatment in the Veterans Health Administration.

Hepatitis B virus (HBV) reactivation may occur with high risk immunosuppression, such as anti-cluster of differentiation (CD)20 antibodies (Abs). Appropriate HBV prophylaxis during anti-CD20 Ab therapy averts hepatitis, chemotherapy disruption, and death. Serologic evidence of prior HBV exposure is present in one in nine veterans in the Veterans Health Administration (VHA). In 2014, most (61%-73%) patients in the VHA who were receiving anti-CD20 Ab treatment underwent HBV testing, yet <20% of eligible patients received HBV antiviral prophylaxis. We aimed to prevent HBV reactivation by increasing HBV testing and antiviral treatment rates among anti-CD20 Ab recipients through prospective interventions. A multidisciplinary team of clinicians, pharmacists, and public health professionals developed comprehensive prevention systems, including national seminars/newsletters/websites; pharmacy criteria for HBV screening/treatment prior to anti-CD20 Ab use; changes to national formulary restrictions to expand HBV prophylaxis prescribing authority; Medication Use Evaluation Tracker to identify omissions; national e-mail alert to all VHA oncology providers detailing specific testing and HBV antiviral treatment needs; and a voluntary electronic medical record "order check" used at interested facilities (n = 11) to automatically assess pretreatment HBV testing and antiviral treatment and only generate a reminder to address deficiencies. Analysis of monthly data from June 2016 through September 2017 among anti-CD20 Ab recipients revealed pre-anti-CD20 Ab treatment HBV testing increased to 91%-96% and appropriate HBV antiviral prophylaxis to 76%-85% nationally following implementation of the intervention. Medical centers using the voluntary electronic medical record order check increased HBV testing rates to 93%-98% and HBV antiviral prophylaxis rates to 99%. Conclusion: Multimodal intervention systems to prevent HBV reactivation among VHA patients receiving anti-CD20 Ab therapies increased national rates of HBV testing to >90% and antiviral prophylaxis to >80%.

Ibrutinib-associated tumor lysis syndrome in chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma: A case series and review of the literature.

Background Tumor lysis syndrome results when intracellular contents are released during cell lysis. Ibrutinib, a Bruton tyrosine kinase inhibitor, is used for the treatment of chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenström's macroglobulinemia, mantle cell lymphoma, and marginal zone lymphoma. Tumor lysis syndrome caused by ibrutinib therapy is potentially life threatening, but is rare and not often reported in clinical trials. Objective The purpose of this case series is to describe the occurrence of tumor lysis syndrome in two patients initiated on ibrutinib, and to highlight the importance of close monitoring during therapy. Discussion One patient with chronic lymphocytic leukemia/small lymphocytic lymphoma and one patient with mantle cell lymphoma developed laboratory and clinical tumor lysis syndrome following initiation of ibrutinib therapy. Assessment with the Naranjo Adverse Drug Reaction Probability Scale indicated one probable relationship and one possible relationship between ibrutinib therapy and tumor lysis syndrome. There were additional factors that may have confounded the laboratory and clinical factors observed, including baseline laboratory values and concurrent medications. Both patients were managed with supportive therapies. A literature review identified five additional reported cases of tumor lysis syndrome following ibrutinib therapy. Conclusion This case series identifies one patient with a probable relationship and one patient with a possible relationship between the development of tumor lysis syndrome and treatment with ibrutinib. Although uncommon, proper attention should be given to monitoring for this adverse drug reaction and appropriate follow-up should occur despite ibrutinib's ease of administration.

PCA safety data review after clinical decision support and smart pump technology implementation.

INTRODUCTION: Medication errors account for 20% of medical errors in the United States with the largest risk at prescribing and administration. Analgesics or opioids are frequently used medications that can be associated with patient harm when prescribed or administered improperly. In an effort to decrease medication errors, Duke University Hospital implemented clinical decision support via computer provider order entry (CPOE) and "smart pump" technology, 2/2008, with the goal to decrease patient-controlled analgesia (PCA) adverse events. METHODS: This project evaluated PCA safety events, reviewing voluntary report system and adverse drug events via surveillance (ADE-S), on intermediate and step-down units preimplementation and postimplementation of clinical decision support via CPOE and PCA smart pumps for the prescribing and administration of opioids therapy in the adult patient requiring analgesia for acute pain. DISCUSSION: Voluntary report system and ADE-S PCA events decreased based upon 1000 PCA days; ADE-S PCA events per 1000 PCA days decreased 22%, from 5.3 (pre) to 4.2 (post) (P = 0.09). Voluntary report system events decreased 72%, from 2.4/1000 PCA days (pre) to 0.66/1000 PCA days (post) and was statistically significant (P < 0.001). There was a difference in the ADE-S data for causality (P < 0.0001) with sleep apnea and renal insufficiency approaching significance. Voluntary report system safety event were statistically significant for obesity [body mass index (BMI) ≥30] and weight. CONCLUSION: This study demonstrated a decrease in PCA events between time periods in both the ADE-S and voluntary report system data, thus supporting the recommendation of clinical decision support via CPOE and PCA smart pump technology.

Everolimus: a new mammalian target of rapamycin inhibitor for the treatment of advanced renal cell carcinoma.

OBJECTIVE: To review clinical trials and main characteristics of everolimus, with focus on treatment of advanced renal cell carcinoma. DATA SOURCES: Pertinent data were identified primarily through a search of MEDLINE and PubMed (1966-November 2010) using the primary search terms everolimus, RAD001, renal cell carcinoma, and mTOR inhibitors. STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the safety and efficacy of everolimus in patients with cancer were evaluated, including Phase 1, 2, and 3 trials. Preference was given to Phase 2 and 3 studies evaluating use of everolimus in patients with renal cell carcinoma. DATA SYNTHESIS: Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor approved for the management of patients with advanced renal cell carcinoma who progressed on tyrosine kinase inhibitor therapy. Actions of everolimus within the mTOR pathway result in decreased protein synthesis and cell cycle arrest, as well as decreased angiogenesis. A usual starting dose for patients with renal cell carcinoma is 10 mg daily. Everolimus undergoes extensive hepatic metabolism, primarily through the CYP3A4 isoenzyme, which predisposes it to drug interactions with inducers and inhibitors of this enzyme. Most commonly reported adverse events associated with everolimus include anemia, hyperglycemia, hypercholesterolemia, mucositis, fatigue, and rash. Approval of everolimus was based on the results of a Phase 3 trial that demonstrated an increase in median progression-free survival by 2.1 months in patients receiving everolimus therapy as compared to placebo. The drug was recently added to the National Comprehensive Cancer Network guidelines as a treatment option for patients with advanced renal cell carcinoma who have progressed on tyrosine kinase therapy. CONCLUSIONS: Based on a review of the currently available literature, everolimus provides a safe and efficacious treatment option for patients with renal cell carcinoma who have progressed on treatment with sunitinib and/or sorafenib.

Lifestyle factors, hormonal contraception, and premenstrual symptoms: the United Kingdom Southampton Women's Survey.

OBJECTIVE: To estimate the prevalence of premenstrual symptoms in women from the general population in Southampton, U.K., and examine their association with lifestyle factors and contraceptive use. METHODS: This was a cross-sectional survey in the city of Southampton, U.K., of 974 women aged 20-34 years (53% of the 1841 women invited to participate). The survey consisted of interviews, questionnaires, and completion of a prospective 6-week menstrual symptom diary recording on a daily basis the presence and severity of 11 common premenstrual symptoms. Premenstrual symptoms were identified from the diaries by two clinicians who reviewed them independently using a predefined algorithm to assess the onset and decline of symptoms in relation to the start of menstruation. RESULTS: Of the women surveyed, 24% were considered to have premenstrual symptoms (95% confidence interval [CI] 21-27). Women were less likely to have symptoms if they had higher levels of educational attainment and suffered less from stress. No associations were found between premenstrual symptoms and diet, alcohol, or strenuous exercise nor after adjustment for other factors, with age, smoking, or body mass index (BMI). Use of any form of hormonal contraceptives was associated with a lower prevalence of premenstrual symptoms (prevalence ratio 0.66, 95% CI 0.52-0.84). CONCLUSIONS: Premenstrual symptoms were common in this cohort. Use of hormonal contraceptive methods was associated with a lower prevalence of these symptoms.

Systematic review: reliability of compendia methods for off-label oncology indications.

BACKGROUND: The Centers for Medicare & Medicaid Services limit coverage of cancer drugs for off-label indications to indications listed in specified compendia. PURPOSE: To assess whether compendia provide comprehensive, research-based, and timely information for off-label prescribing in oncology. DATA SOURCES: 6 drug compendia, English-language literature searches of MEDLINE and the Cochrane Central Register of Controlled Trials from 2006 and 2008, and American Society of Clinical Oncology annual meeting abstracts from 2004 to 2007. Data Assessment: The compendia's stated methods, literature related to off-label indications of 14 cancer drugs in 2006, updated literature related to 1 off-label indication between 2006 and 2008, and completeness of compendia content and citations were assessed. DATA SYNTHESIS: The compendia's stated methods varied greatly from their actual practices. Compendia cited little of the available evidence, often neither the most recent nor that of highest methodological quality. Compendia differed in evidence cited, terminology, detail, presentation, and referencing. For the 14 off-label indications studied, the compendia differed in the indications included and whether and how they recommended particular agents for particular types of cancer. Update schedules varied, and documentation practices made it difficult to determine whether and when compendia content was updated. For 1 indication, compendia citations did not increase between 2006 and 2008 despite newly published articles. LIMITATIONS: The 2006 analysis was limited to 14 off-label indications; the 2008 update examined 1 indication. Only off-label indications for cancer drugs were included, and results cannot be generalized to noncancer drugs or indications. CONCLUSION: Oncologists rely on compendia for up-to-date access to evidence and reimbursement information for off-label indications. Current compendia lack transparency, cite little current evidence, and lack systematic methods to review or update evidence.

Clinical utility of rituximab in chronic graft-versus-host disease.

OBJECTIVE: To evaluate the use of rituximab in the clinical management of steroid-refractory chronic graft-versus-host disease (GVHD). DATA SOURCES: Literature was accessed through MEDLINE and International Pharmaceutical Abstracts (1990-September 2008), both indexed and nonindexed citations, using the terms rituximab, graft-versus-host disease, monoclonal antibodies, and CD20. In addition, reference citations from the publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles discussing rituximab as a therapeutic option in the treatment of GVHD that were published in English and enrolled human study participants were evaluated. DATA SYNTHESIS: Rituximab is a genetically engineered chimeric murine monoclonal antibody that binds to the CD20 differentiation antigen found on B-lymphocytes. GVHD is the leading cause of procedural-related morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Chronic GVHD (cGVHD) occurs in up to 70% of individuals undergoing HSCT, and approximately 40% of those patients are refractory to conventional T-lymphocyte-directed therapies. Limited treatments are available for individuals with steroid-refractory cGVHD. Rituximab therapy in individuals with extensive cGVHD has demonstrated clinical efficacy with manageable toxicities in retrospective and prospective studies. CONCLUSIONS: Available data suggest that rituximab is a treatment option for patients with extensive steroid-refractory cGVHD. Rituximab may be particularly effective for individuals with steroid-refractory cGVHD manifesting as thrombocytopenia or with sclerodermatous, cutaneous, and rheumatologic involvement.

Treatment options in imatinib-resistant chronic myelogenous leukemia.

OBJECTIVE: To discuss new therapeutic options available in the treatment of chronic myelogenous leukemia (CML) in patients who failed or were intolerant to imatinib therapy. DATA SOURCES: Literature was accessed via MEDLINE (1966-May 2007), EMBASE (1991-3rd quarter 2007), the Proceedings of the American Society of Hematology (2000-2006), and the Proceedings of the American Society of Clinical Oncology (2000-2007). Search terms included imatinib, dasatinib, nilotinib, and chronic myelogenous leukemia. STUDY SELECTION AND DATA EXTRACTION: Meeting abstracts and studies that reported preclinical and Phase 1, 2, and 3 trials published in English are included. DATA SYNTHESIS: Imatinib is the standard of care for CML; however, some patients develop resistance or are intolerant to the drug. Phase 1 and 2 clinical data for the more potent tyrosine kinase inhibitors, dasatinib and nilotinib, are promising. Hematologic and cytogenetic responses are reported with both. There does not appear to be cross-resistance between the drugs, although neither is effective against all mutations of the hallmark molecular marker, the Philadelphia chromosome. Novel agents are also being examined for the treatment of patients with CML, including aurora kinase and farnesyl transferase inhibitors, as well as combination therapies. CONCLUSIONS: Dasatinib and nilotinib are second-line options for patients who have CML and are resistant or intolerant to imatinib. Toxicity profiles between agents may differ. Clinical trials with these drugs and others are ongoing.

Role of lenalidomide in the treatment of multiple myeloma and myelodysplastic syndrome.

OBJECTIVE: To evaluate lenalidomide in the treatment of multiple myeloma and myelodysplastic syndrome (MDS). DATA SOURCES: Clinical literature was accessed through MEDLINE (1966-August 2005), Science Citation Index (1980-August 2005), and Proceedings of the American Society of Hematology (2000-2004). DATA SYNTHESIS: New analogs of thalidomide have been synthesized that are more potent and less toxic. Lenalidomide (CC-5013) is currently in Phase III trials for the treatment of multiple myeloma and MDS. Phase II trials demonstrated lenalidomide's efficacy in patients refractory to thalidomide. The full potential of this agent has yet to be proven, but preliminary data seem promising. CONCLUSIONS: Lenalidomide is a potent immunomodulating drug that offers different mechanisms of action and therapeutic potential for the treatment of multiple myeloma, MDS, and other malignancies.